Abstract: Disclosed is a process for preparing a pharmacologically active compound, in which at least one internal conjugation site of an Fc domain sequence is selected that is amenable to conjugation of an additional functional moiety by a defined conjugation chemistry through the side chain of an amino acid residue at the conjugation site. An appropriate amino acid residue for conjugation may be present in a native Fc domain at the conjugation site or may be added by insertion (i.e., between amino acids in the native Fc domain) or by replacement (i.e., removing amino acids and substituting different amino acids). In the latter case, the number of amino acids added need not correspond to the number of amino acids removed from the previously existing Fc domain. This technology may be used to produce useful compositions of matter and pharmaceutical compositions containing them.
Type:
Grant
Filed:
July 10, 2015
Date of Patent:
January 29, 2019
Assignee:
AMGEN INC.
Inventors:
Colin V. Gegg, Kenneth W. Walker, Leslie P. Miranda, Fei Xiong
Abstract: Disclosed is an isolated antigen binding protein, such as but not limited to, an antibody or antibody fragment. Also disclosed are pharmaceutical compositions and medicaments comprising the antigen binding protein, isolated nucleic acid encoding it, vectors, host cells, and hybridomas useful in methods of making it. In some embodiments the antigen binding protein comprises one to twenty-four pharmacologically active chemical moieties conjugated thereto, such as a pharmacologically active polypeptide.
Type:
Grant
Filed:
January 12, 2017
Date of Patent:
January 29, 2019
Assignee:
AMGEN INC.
Inventors:
Kenneth W. Walker, Yue-Sheng Li, Thomas Charles Boone, George Doellgast, HoSung Min, Jane Talvenheimo, Taruna Arora, Frederick W. Jacobsen
Abstract: A method for assessing the risk of potential adverse effects for a human patient receiving a CD19×CD3 bispecific antibody is provided. The method comprises determining the total B count in the patient, and identifying a B cell number indicative of a patient at risk of potential adverse effects from the antibody. The method further provides a dosing schedule for administering the antibody to the patient identified as at risk of potential adverse effects. Also provided is a pharmaceutical package or kit comprising a first dose and a second dose, and optionally a third dose, of the CD19×CD3 bispecific antibody as defined in the methods/dosage regimen of the disclosure.
Abstract: Provided herein are myeloid cell leukemia 1 protein (Mcl-1) inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.
Type:
Application
Filed:
September 5, 2018
Publication date:
January 24, 2019
Applicant:
Amgen Inc.
Inventors:
Sean P. BROWN, Yunxiao LI, Mike Elias LIZARZABURU, Brian S, LUCAS, Nick A. PARAS, Joshua TAYGERLY, Marc VIMOLRATANA, Xianghong WANG, Ming YU, Manuel ZANCANELLA, Liusheng ZHU, Ana GONZALEZ BUENROSTRO, Zhihong LI
Abstract: Disclosed herein is a wearable drug delivery device including a container filled at least partially with a drug including at least one of a PCSK9 (Proprotein Convertase Subtilisin/Kexin Type 9) specific antibody, a granulocyte colony-stimulating factor (G-CSF), a sclerostin antibody, or a calcitonin gene-related peptide (CGRP) antibody. The wearable drug delivery device may include a needle and an insertion mechanism configured to insert the needle into a patient. A fluid pathway connector may define a sterile fluid flowpath between the container and the insertion mechanism. Optionally, a cannula initially disposed about the needle may be included. The cannula may be retained in the patient at an injection site created by the needle after the needle is withdrawn from the patient. Methods of assembly and operation are also provided.
Type:
Application
Filed:
February 13, 2017
Publication date:
January 24, 2019
Applicant:
Amgen Inc.
Inventors:
Scott R. GIBSON, Sheldon B. MOBERG, Basel Hasan TAHA, Margaux Frances BOYAVAL, Mark A. DESTEFANO, John C. LOVE, Ian B. HANSON, Paul F. BENTE, IV, Matthew J. CLEMENTE, Rajan RAMASWAMY, Daniel S. CODD, Scott BEAVER, Kevin L. BOKELMAN, Sean M. O'CONNOR, Robert DECKER, Gautam N. SHETTY, Ryan M. AGARD, Nicholas J. CICCARELLI, Daniel DAVENPORT
Abstract: The present invention relates to methods of upregulating the high mannose glycoform content of a recombinant protein during a mammalian cell culture by manipulating the mannose to total hexose ratio in the cell culture media formulation.
Abstract: Provided herein are compounds that are useful intermediates that may used to synthesize myeloid cell leukemia 1 protein (Mcl-1) inhibitors. Also provided are Mcl-1 inhibitors, methods of their preparation, related pharmaceutical compositions, and methods of using the same. For example, provided herein are compounds of Formula I, and pharmaceutically acceptable salts thereof and pharmaceutical compositions containing the compounds. The compounds and compositions provided herein may be used, for example, in the treatment of diseases or conditions, such as cancer.
Type:
Application
Filed:
September 6, 2018
Publication date:
January 17, 2019
Applicant:
Amgen Inc.
Inventors:
Sean P. BROWN, Yunxiao LI, Mike Elias LIZARZABURU, Brian S. LUCAS, Nick A. PARAS, Joshua TAYGERLY, Marc VIMOLRATANA, Xianghong WANG, Ming YU, Manuel ZANCANELLA, Liusheng ZHU, Ana GONZALEZ BUENROSTRO, Zhihong LI
Abstract: The present invention relates to BCMA (B-Cell Maturation Antigen) antigen binding proteins, such as antibodies, polynucleotide sequences encoding said antigen binding proteins, and compositions and methods for diagnosing and treating diseases. The present invention also relates to BCMA antibody drug conjugates.
Type:
Application
Filed:
December 11, 2015
Publication date:
January 10, 2019
Applicant:
Amgen Inc.
Inventors:
Richard J. ARMITAGE, Michelle BLAKE, William C. FANSLOW, III, Jason Charles O'NEILL, Gunasekaran KANNAN, Jiangchun XU, Mark Edward TOMETSKO
Abstract: Methods of modulating the properties of a cell culture expressing a protein of interest are provided. In various embodiments the methods relate to the overexpression of proteins involved in the N-glycosylation pathway.
Abstract: The disclosed methods are directed to detecting polypeptide fragments (“clips”) of parental polypeptides. Parental polypeptides and clips are optionally denatured and then fractionated using a matrix. After a first elution (high molecular weight fraction), an additional elution step retrieves a low molecular weight fraction containing clips. If the clips are an appropriate size for the targeted detection method, such as mass spectrometry, then analysis of this fraction proceeds separately from the high molecular weight fraction, or the clips fraction is mixed with the proteolyzed high molecular weight fraction before analysis. However, if the clips are too large for the intended analytical method(s), then the clips are also proteolyzed. The digested high molecular weight and low molecular weight fractions can be analyzed separately or combined. Analysis of combined samples favors clip quantitation because the clips are analyzed together with the remaining counterpart of the parental polypeptide.
Type:
Application
Filed:
June 29, 2018
Publication date:
January 3, 2019
Applicant:
AMGEN INC.
Inventors:
Da REN, Izydor APOSTOL, Alexander Julian VEACH
Abstract: The present invention relates to methods, compositions, and kits for using placental growth factor (PLGF) as an informative biomarker in determining the clinical benefit to renal cell carcinoma patients by treatment with a VEGFR inhibitor and an Ang2 inhibitor.
Type:
Application
Filed:
June 22, 2016
Publication date:
January 3, 2019
Applicant:
AMGEN INC.
Inventors:
Abraham Antonio ANDERSON, Bruce A. BACH, Cheryl A. PICKETT-GIES, Michael B. BASS
Abstract: The present invention relates to methods of upregulating the high mannose glycoform content of a recombinant protein during a mammalian cell culture by manipulating the mannose to total hexose ratio in the cell culture media formulation.
Abstract: The present invention provides long-term stable formulations of a lyophilized therapeutic peptibody and methods for making a lyophilized composition comprising a therapeutic peptibody.
Type:
Grant
Filed:
January 29, 2016
Date of Patent:
January 1, 2019
Assignee:
AMGEN INC.
Inventors:
William J. Callahan, Richard L. Remmele, Jr., Gayathri Ratnaswamy, Ramil F. Latypov, Dingjiang Liu
Abstract: The present invention provides compounds of Formula (I), and pharmaceutically acceptable salts thereof, that are inhibitors of voltage-gated sodium channels, in particular Nav1.7. The compounds are useful for the treatment of diseases associated with the activity of sodium channels such as pain disorders, cough, and itch. Also provided are pharmaceutical compositions containing compounds of the present invention.
Type:
Application
Filed:
December 19, 2016
Publication date:
December 27, 2018
Applicant:
AMGEN INC.
Inventors:
Matthew WEISS, Thomas DINEEN, Benjamin C. MILGRAM
Inventors:
Brian Stonecipher, Craig Lester, R. Paul Mounce, Eva Stump, Michel D. Arney, Maxwell Franklin Bischoff, Laurie Burns, Gregg Allen Flender, Barbara Hartigan, Gaurav Rohatgi, Bryce George Rutter, Megan Marie Rutter, Kristin Leigh Sjo-Gaber